Role of inflammatory pathways, blood mononuclear cells, and gut-derived bacterial products in alcohol dependence
(2014) Biological Psychiatry — Vol. 76, n° 9, p. 725-733 (2014)
Files
pdfdocument.pdf
Restricted Access - Adobe PDF
- 1.45 MB
Details
- Authors
- Abstract
- Background: Inflammation might play a role in the development of several psychiatric diseases. However, the origins of processes that mediate inflammation remain unknown. We previously reported, in alcohol-dependent (AD) subjects, increased intestinal permeability, elevated blood lipopolysaccharides (LPS) levels, and low-grade systemic inflammation associated with psychological symptoms of alcohol dependence. In this study, we tested during detoxification peripheral blood mononuclear cells (PBMCs) inflammatory responses to gut-derived bacterial products and its relation to alcohol-craving. Methods: Sixty-three actively-drinking non-cirrhotic AD subjects were tested at the beginning (day 2) and end (day 18) of alcohol detoxification and compared with 14 healthy subjects. Activation of various intracellular signaling pathways by gut-derived bacterial products was analyzed by qPCR, Western blotting and DNA binding assays (for transcription factors). Toll-like receptors activation was assessed by cell cultures. Results: In addition to LPS, we showed that peptidoglycans (PGN) may also cross the gut barrier to reach the systemic circulation. Both activate their respective Toll-like receptors in PBMCs. Chronic alcohol consumption inhibited the nuclear factor kappa B pro-inflammatory cytokine pathway, but activated the mitogen-activated protein kinase/activator protein 1 pathway, together with the inflammasome complex. This resulted in increased mRNA and plasma levels of interleukin (IL)-8, IL-1β, and IL-18. Activated pro-inflammatory pathways,in particular IL-8 and IL-1β, were positively correlated with alcohol consumption and alcohol-craving scores. Short-term alcohol withdrawal was associated with the recovery of LPS- but not PGN-dependent receptors. Conclusions: LPS and PGN from the gut microbiota stimulate specific inflammatory pathways in PBMCs that are correlated with alcohol craving.
- Affiliations
Citations
Leclercq, S., De Saeger, C., Delzenne, N., de Timary, P., & Starkel, P. (2014). Role of inflammatory pathways, blood mononuclear cells, and gut-derived bacterial products in alcohol dependence. Biological Psychiatry, 76(9), 725-733. https://doi.org/10.1016/j.biopsych.2014.02.003 (Original work published 2014)